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Hereditary salt-losing syndromes have been ascribed to loss of function mutations in the \u03b1-, \u03b2-, or \u03b3-ENaC subunit genes, whereas gain of function mutations (located in the COOH terminus of the \u03b2- or \u03b3-subunit) result in hypertension due to Na<jats:sup>+<\/jats:sup>retention (Liddle\u2019s syndrome). In mice, gene-targeting experiments have shown that, in addition to the kidney salt-wasting phenotype, ENaC was essential for lung fluid clearance in newborn mice. Disruption of the \u03b1-subunit resulted in a complete abolition of ENaC-mediated Na<jats:sup>+<\/jats:sup>transport, whereas knockout of the \u03b2- or \u03b3-subunit had only minor effects on fluid clearance in lung. Disruption of each of the three subunits resulted in a salt-wasting syndrome similar to that observed in humans.<\/jats:p>","DOI":"10.1152\/ajpgi.1999.276.3.g567","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T09:53:08Z","timestamp":1514109188000},"page":"G567-G571","source":"Crossref","is-referenced-by-count":36,"title":["V. 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